Synthesis and topoisomerase I inhibitory activity of a novel diazaindeno[2,1-b]phenanthrene analogue of Lamellarin D
Synthesis and topoisomerase I inhibitory activity of a novel diazaindeno[2,1-b]phenanthrene analogue of Lamellarin D
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DOI：
10.1016/j.bmc.2011.06.056
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发表时间：
2011-08-15
影响因子：
3.5
通讯作者：
Dallavalle, Sabrina
中科院分区：
文献类型：
--
作者：
Cananzi, Salvatore;Merlini, Lucio;Dallavalle, Sabrina
设计并合成了一种新的5-氧杂-6a，8-二氮茚并[2，1-B]菲-7-酮骨架，作为细胞毒性海洋生物碱Lamellarin D的活性类似物。该设计基于片螺素D与DNA-拓扑异构酶I可切割复合物相互作用位点的分子建模，而合成利用吲哚到β-咔啉酮核的简单Friedel-Crafts环化。该产物对人非小细胞肺癌H460细胞具有拓扑异构酶I的毒性和亚微摩尔细胞毒活性。(C)2011爱思唯尔有限公司版权所有。
A novel 5-oxa-6a,8-diazaindeno[2,1-b]phenanthren-7-one scaffold was designed and synthesized as an active analogue of the cytotoxic marine alkaloid Lamellarin D. The design was based on molecular modeling of the site of interaction of Lamellarin D with DNA-topoisomerase I cleavable complex, whereas the synthesis capitalized on a simple Friedel-Crafts cyclization of indole to a beta-carbolinone nucleus. The product exhibited topoisomerase I poisoning activity and submicromolar cytotoxicity on human non-small cell lung cancer H460 cell line. (C) 2011 Elsevier Ltd. All rights reserved.